Wnt和类固醇通路控制谷氨酸信号通过调节成骨细胞的细胞中谷氨酰胺合成酶活性。
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Olkku, Mahonen
Wnt和类固醇通路控制谷氨酸信号通过调节成骨细胞的细胞中谷氨酰胺合成酶活性。
骨头。2008年9月,43 (3):483 - 93。doi: 10.1016 / j.bone.2008.04.016。2008年5月7日Epub。
- PubMed ID
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18555765 (在PubMed]
- 文摘
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谷氨酸信号最近发现功能也在中枢神经系统,特别是在骨头。谷氨酸转化为谷氨酰胺的谷氨酰胺合成酶(GS),因此能够调节细胞内浓度的谷氨酸。我们以前描述的GS表达的诱导糖皮质激素(gc)在人类osteoblast-like细胞。除此之外观察,机制控制骨GS是未知的。因此,本研究的目的是探讨进一步的规定GS成骨细胞的细胞。我们发现维生素D抑制基底,甚至更有效率,GC-stimulated GS活动影响mRNA和蛋白浓度的过氧化氢酶在人类osteoblast-like mg - 63细胞。在成骨细胞来源于鼠骨髓干细胞(rMSCs)、GS活性诱导成骨的文化条件包括相应的gc。同样在这些主要细胞,明显抑制GS活性维生素D。此外,规范化Wnt信号通路被描述为消极的GS活动的监管机构。所有这些变化在GS活性是反映细胞内谷氨酸浓度。 Our results provide novel evidence that GS activity and expression are regulated by several different signalling pathways in osteoblastic cells. Therefore, GS is a strategic enzyme in controlling glutamate concentration in bone environment: GCs decreased the amount of this signalling molecule while vitamin D and Wnt signalling pathway increased it. Interestingly, GS activity and expression declined rapidly when the rMSC derived osteoblasts began to mineralize. Due to its downregulation during osteoblast mineralization, GS could be held as a marker for osteoblast development. Further supporting this, GS activity was stimulated and intracellular glutamate concentration maintained by the N-methyl-d-aspartate (NMDA) type glutamate receptor antagonist MK801, which inhibited osteogenic differentiation of the rMSCs. GS, a novel target for both steroidal and Wnt pathways in bone, might be a central player in the regulation of osteoblastogenesis and/or intercellular signal transmission. Therefore, the proper understanding of the interplay of these three signalling cascades, i.e., steroidal, Wnt, and glutamate signalling, gives vital information on how bone cells communicate together aiming to keep bone healthy.